Synthesis and evaluation of fuligocandin b derivatives with activity for overcoming TRAIL resistance

Midori A. Arai, Ayaka Masuda, Akiko Suganami, Yutaka Tamura, Masami Ishibashi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway induces apoptosis in cancer cells but not in normal cells. Therefore, this pathway has attracted attention regarding possible clinical treatment of cancer. However, many cancer cells demonstrate TRAIL resistance. To overcome this problem, small molecules that sensitize cancer cells to TRAIL are desired. Heterocyclic derivatives of the natural product, fuligocandin B (2), with activity for overcoming TRAIL resistance were synthesized, and their activity was evaluated. Of the synthetic molecules, the quinoline derivative (10g) showed potent activity against TRAIL-resistant gastric adenocarcinoma cells. After a docking study of the target protein valosin-containing protein, 7′-amino fuligocandin B (10m) was designed and synthesized. Compound 10m also showed good activity for overcoming TRAIL resistance. 10m produced a 49.7% difference in viability with TRAIL at 30µM compared to without TRAIL. This activity was better than that of fuligocandin B (2).

Original languageEnglish
Pages (from-to)810-817
Number of pages8
JournalChemical and Pharmaceutical Bulletin
Issue number8
Publication statusPublished - 2018
Externally publishedYes


  • Cancer
  • Cytotoxicity
  • Inhibitor
  • Natural product
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

ASJC Scopus subject areas

  • General Chemistry
  • Drug Discovery


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